Oral or nasal delivery of a medicament using an inhalation device is a particularly attractive method of drug administration as these devices are relatively easy for a patient to use discreetly and in public. As well as delivering medicament to treat local diseases of the airway and other respiratory problems, they have more recently also been used to deliver drugs to the bloodstream via the lungs, thereby avoiding the need for hypodermic injections.
It is common for dry powder formulations to be pre-packaged in blisters each of which contains a single dose of powder which has been accurately and consistently measured. The blister protects each dose from the ingress of moisture and penetration of gases such as oxygen in addition to shielding the dose from light and UV radiation all of which can have a detrimental effect on the medicament and on the operation of an inhaler used to deliver the medicament to a patient.
A blister pack generally comprises a base having one or more spaced apart cavities defining blisters to receive individual doses of medicament and a lid in the form of a generally planar sheet that is sealed to the base except in the region of the cavities. The base material is typically a laminate comprising a polymer layer in contact with the drug, a soft tempered aluminium layer and an external polymer layer. The aluminium provides the moisture and oxygen barrier, whilst the polymer aids adhesion of the aluminium to the heat seal lacquer and provides a relatively inert layer in contact with the drug. Soft tempered aluminium is ductile so that it can be “cold formed” into a blister shape. It is typically 45 μm thick. The outer polymer layer provides additional strength and toughness to the laminate.
The lid material is typically a laminate comprising a heat seal lacquer, a hard rolled aluminium layer and an external lacquer layer. The heat seal lacquer layer bonds to the polymer layer of the base foil laminate during heat-sealing to provide a seal around the top of the blister cavity. The hard temper foil is relatively frangible to enable it to be pierced easily by a piercing element forming part of an inhalation device, to create one or more openings in the lid. These openings enable air or gas to flow through the blister, thereby entraining the dry powder and causing it to be removed from the blister. The powder can then be deagglomerated to form a respirable cloud and made available for inhalation by the user.
Inhalation devices that receive a blister pack or strip of blisters are known. Actuation of the device causes a mechanism to index and pierce a blister so that when the device is used, air is drawn through the blister entraining the dose, which is then carried out of the blister through the device and via the patient's airway down into the lungs. One such device is known from one of the Applicant's own European patent No. 1684834B1, which is incorporated in its entirety herein by reference.
The airflow can be created by inhalation of the user. Such inhaler devices are generally known as passive devices. Alternatively, the inhaler may include a source of energy such as a mechanical pump or canister of pressurised gas to generate pressure or suction. The air or gas flow in these active devices can potentially be greater than that in a passive device, and more repeatable. This can give better and more consistent blister emptying.
It has been found that it is difficult to control the size and configuration of the opening that is pierced in a blister lid because the foil may not always tear or burst in a consistent way. However, the means by which the blister is pierced is of critical importance in the performance of a dry powder inhalation device.
It is common for problems to occur because, when the lid is pierced, foil flaps are formed that are pushed into the blister. These can either trap powder in the blister or obscure the opening. It will be appreciated that it is beneficial to form a large opening in the blister lid to enable a sufficient flow of air through the blister, and to enable the removal of agglomerates that may have formed in the powder during storage. However, a large opening in the blister means that the foil flaps are large and so are more likely to trap powder and hinder airflow. Furthermore, more powder may be trapped depending upon the orientation in which the device is being held when piercing takes place.
Although the Applicant's own earlier application EP1868674A, which is incorporated herein by reference, provides a blister piercing member that addresses the problem of powder being trapped in the blister by a foil flap cut in the blister lid, many powders are particularly cohesive in nature and form agglomerates in the blister that can still become trapped more easily than less cohesive powders where agglomerates are less easily formed. Therefore, there is a desire to further minimise the possibility of powder becoming trapped behind a foil flap, particularly when the dose is formed from a more cohesive powder that is more likely to agglomerate. There is also a desire to provide a blister piercing element which provides a more consistent pierce and in which the likelihood of powder becoming trapped is less dependent on the orientation in which the inhaler is in when piercing occurs.